The effect of genetic variation in chemokines and their receptors on HIV transmission and progression to AIDS

The pivotal discovery that two chemokine receptors, CCR5 and CXCR4, serve a long with the T-cell receptor-interacting CD4 molecule as the principal co- receptors for HIV-1 entry stimulated a search for common genetic polymorphi sm in their genes which might affect the course of AIDS. Four mutational va riants, CCR5-Delta 32, CCR5-P1, CCR2-64I and SDF1-3'A were discovered to pl ay a regulatory role in HIV-1 infection, in the rate of progression to AIDS or both. Plausible physiological mechanisms to explain the population gene tic association by these alleles have been advanced and are discussed criti cally here. Genetic ablation of AIDS progression by chemokine receptor and Ligand gene variants has catalyzed development of novel therapies targeting the virus-co-receptor interaction. The functional and therapeutic implicat ions of these AIDS restriction genes for disease progression and interventi on are explored in this review.